The overall objective of this research is to clarify the relationship between structure and function in regulatory proteins. To do this, three main areas will be explored: (a) the further clarification of the nature of protein conformational changes which occur as the result of interaction of ligands with proteins, (b) the correlation of the in vitro properties of proteins with their in vivo control of biological systems, and (c) the study of neural systems, particularly in relation to the role of receptor proteins. The role of conformational changes in enzyme control, repressors, membranes and receptors is well established in some cases and widely assumed in others. The next stage in our understanding will require more detailed study of protein structure and the development of quantitative relationships. These objectives will be pursued in various specific systems which include the enzyme phosphoribosyl ATP synthetase (the first enzyme of the histidine pathway), CTP synthetase (the last enzyme in the CTP pathway), glyceraldehyde-3-phosphate dehydrogenase from species as diverse as yeast and man, and chemotaxis as an example of a primitive receptor-communication system. Theoretical principles will be developed and tested on whichever of these systems is most amenable and most pertinent for the specific experiment. BIBLIOGRAPHIC REFERENCES: Receptor interactions in a signalling system: competition between ribose receptor and galactose receptor in the chemotaxis response. Proc. Nat. Acad. Sci. USA 73:762-766 (1976). P. G. Strange and D. E. Koshland, Jr.; Bacterial chemotaxis as a simple model for a sensory system. Trends in Biochemical Sciences L: 1-3 (1976). D. E. Koshland, Jr.